This invention relates to novel aminopropylaminobleomycin derivatives.
The term bleomycin refers to a family of structurally related antitumor antibiotic substances discovered in 1966 by Umezawa, one of the present inventors, and collaborators [J. of Antibiotics, 19A, p. 200 (1966)]. Bleomycin is produced by Streptomyces verticillus, an Actinomycete, and is a mixture of basic water-soluble glycopeptides each of which is capable of readily chelating one atom of divalent copper. In ordinary culture, 16 members of the bleomycin family are produced and are each isolated [e.g. Umezawa et al., Journal of Antibiotics, 19A, p. 210 (1966)]. Various bleomycins are also disclosed in U.S. Pat. No. 3,922,262 and U.S. Pat. No. Re. 30,451. Because of their distinguished antitumor activity in spite of some undesirable side effects such as pulmonary toxicity, bleomycins have already been widely used in clinical fields of cancer therapy; particularly, they are successfully used in the treatment of squamous cell carcinoma as principal target, skin cancer, head and neck cancer, lung cancer, and malignant lymphoma. It is still desired, however, that bleomycins be further improved in antitumor activity and reduced in side effects, especially in pulmonary toxicity.